TY - JOUR T1 - Prenatal clinical manifestations in individuals with <em>COL4A1/2</em> variants JF - Journal of Medical Genetics JO - J Med Genet SP - 505 LP - 513 DO - 10.1136/jmedgenet-2020-106896 VL - 58 IS - 8 AU - Toshiyuki Itai AU - Satoko Miyatake AU - Masataka Taguri AU - Fumihito Nozaki AU - Masayasu Ohta AU - Hitoshi Osaka AU - Masafumi Morimoto AU - Tomoko Tandou AU - Fumikatsu Nohara AU - Yuichi Takami AU - Fumitaka Yoshioka AU - Shoko Shimokawa AU - Jiu Okuno-Yuguchi AU - Mitsuo Motobayashi AU - Yuko Takei AU - Tetsuhiro Fukuyama AU - Satoko Kumada AU - Yohane Miyata AU - Chikako Ogawa AU - Yuki Maki AU - Noriko Togashi AU - Teruyuki Ishikura AU - Makoto Kinoshita AU - Yusuke Mitani AU - Yonehiro Kanemura AU - Tsuyoshi Omi AU - Naoki Ando AU - Ayako Hattori AU - Shinji Saitoh AU - Yukihiro Kitai AU - Satori Hirai AU - Hiroshi Arai AU - Fumihiko Ishida AU - Hidetoshi Taniguchi AU - Yasuji Kitabatake AU - Keiichi Ozono AU - Shin Nabatame AU - Robert Smigiel AU - Mitsuhiro Kato AU - Koichi Tanda AU - Yoshihiko Saito AU - Akihiko Ishiyama AU - Yushi Noguchi AU - Mazumi Miura AU - Takaaki Nakano AU - Keiko Hirano AU - Ryoko Honda AU - Ichiro Kuki AU - Jun-ichi Takanashi AU - Akihito Takeuchi AU - Tatsuya Fukasawa AU - Chizuru Seiwa AU - Atsuko Harada AU - Yusuke Yachi AU - Hiroyuki Higashiyama AU - Hiroshi Terashima AU - Tadayuki Kumagai AU - Satoshi Hada AU - Yoshiichi Abe AU - Etsuko Miyagi AU - Yuri Uchiyama AU - Atsushi Fujita AU - Eri Imagawa AU - Yoshiteru Azuma AU - Kohei Hamanaka AU - Eriko Koshimizu AU - Satomi Mitsuhashi AU - Takeshi Mizuguchi AU - Atsushi Takata AU - Noriko Miyake AU - Yoshinori Tsurusaki AU - Hiroshi Doi AU - Mitsuko Nakashima AU - Hirotomo Saitsu AU - Naomichi Matsumoto Y1 - 2021/08/01 UR - http://jmg.bmj.com/content/58/8/505.abstract N2 - Background Variants in the type IV collagen gene (COL4A1/2) cause early-onset cerebrovascular diseases. Most individuals are diagnosed postnatally, and the prenatal features of individuals with COL4A1/2 variants remain unclear.Methods We examined COL4A1/2 in 218 individuals with suspected COL4A1/2-related brain defects. Among those arising from COL4A1/2 variants, we focused on individuals showing prenatal abnormal ultrasound findings and validated their prenatal and postnatal clinical features in detail.Results Pathogenic COL4A1/2 variants were detected in 56 individuals (n=56/218, 25.7%) showing porencephaly (n=29), schizencephaly (n=12) and others (n=15). Thirty-four variants occurred de novo (n=34/56, 60.7%). Foetal information was available in 47 of 56 individuals, 32 of whom (n=32/47, 68.1%) had one or more foetal abnormalities. The median gestational age at the detection of initial prenatal abnormal features was 31 weeks of gestation. Only 14 individuals had specific prenatal findings that were strongly suggestive of features associated with COL4A1/2 variants. Foetal ventriculomegaly was the most common initial feature (n=20/32, 62.5%). Posterior fossa abnormalities, including Dandy-Walker malformation, were observed prenatally in four individuals. Regarding extrabrain features, foetal growth restriction was present in 16 individuals, including eight individuals with comorbid ventriculomegaly.Conclusions Prenatal observation of ventriculomegaly with comorbid foetal growth restriction should prompt a thorough ultrasound examination and COL4A1/2 gene testing should be considered when pathogenic variants are strongly suspected.All data relevant to the study are included in the article or uploaded as supplementary information. Additional material is published online only. To view, please visit the journal online. ER -